WO2008105632A1 - Compositions for improving skin conditions comprising alpha-bisabolol as an active ingrdient - Google Patents
Compositions for improving skin conditions comprising alpha-bisabolol as an active ingrdient Download PDFInfo
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- WO2008105632A1 WO2008105632A1 PCT/KR2008/001141 KR2008001141W WO2008105632A1 WO 2008105632 A1 WO2008105632 A1 WO 2008105632A1 KR 2008001141 W KR2008001141 W KR 2008001141W WO 2008105632 A1 WO2008105632 A1 WO 2008105632A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Definitions
- the present invention relates to a composition comprising alpha-bisabolol as active ingredients, exhibiting an excellent improvement effect on skin conditions, immune regulatory effect and anti-obesity effect with stability and safety.
- the color of human skin is ascribed mainly to the concentration and distribution of melanin.
- Melanin is one of phenol-based high molecular weighted biosubstances and plays an important role in preventing skin damage elicited by UV.
- the tyrosinase activity present in melanocyte has reported as a pivotal factor for melanin biosynthesis, tyrosinase plays pivotal role in skin darkening process by converting tyrosine into DOPA and DOPA-quinone, which are intermediate product of melanin polymer generation.
- the main factor of wrinkle formation involves the expression and activity of collagenase, a collagen-degrading enzyme to reduce synthesis and content of collagen.
- Hormone imbalance has become increasingly worse due to environmental pollution and auto exhausts. Because of this, the incidence rate of hair loss has become higher, the incidence age is lowered and a variety of skin diseases such as atopy and psoriasis have occurred due to inducing disharmony of skin immune system. In addition, the number of young obesity patients has rapidly went on increasing because of the change of dietary life such as meat and instant food centered diets.
- compositions comprising ⁇ -bisabolol as an active ingredient allowed to provide compositions for improving skin conditions, anti-oxidation and anti-obesity, having excellent effects and safety.
- composition for improving skin condition comprising ⁇ -bisabolol as an active ingredient, wherein the skin condition is wrinkles, whitening, UV-induced skin damage or hair growth.
- a method for improving skin condition which comprises administering to a subject a composition comprising ⁇ -bisabolol as an active ingredient.
- composition for anti-oxidation comprising ⁇ -bisabolol as an active ingredient.
- method for preventing oxidation which comprises administering to a subject a composition comprising ⁇ -bisabolol as an active ingredient.
- ⁇ - bisabolol for manufacturing a composition for anti-oxidation.
- a composition for anti-obesity comprising ⁇ -bisabolol as an active ingredient.
- a method for suppressing obesity which comprises administering to a subject a composition comprising ⁇ -bisabolol as an active ingredient.
- a use of ⁇ - bisabolol for manufacturing a composition for anti-obesity is provided.
- compositions comprising ⁇ -bisabolol as an active ingredient allowed to provide compositions for improving skin conditions, anti-oxidation and anti-obesity, having excellent effects and safety.
- ⁇ -Bisabolol used as an active ingredient in the present invention is a main active ingredient of chamomile essential oil and monocyclic sesquiterpene alcohol.
- IUPAC name of ⁇ -bisabolol is (2S)-6-methyl-2-[(lR)-4-methyl-l-cyclohex-3-enyl]hept- 5-en-2ol, and a compound derived from plants, represented by the following formula I.
- Chamomile has been generally known to be anti-inflammatory effect, sedative activity and alleviation effect on pain.
- bisabolol as its main component is colorless and transparent liquid having anti-inflammatory effect, wound healing and anti- microbial effect in a cosmetic formulation and has been used to various skin care products.
- ⁇ -Bisabolol used as active ingredients in compositions of this invention may be extracted from natural source, chamomile such as Satureja punctata L or synthesized chemically.
- the ⁇ -bisabolol may be obtained using conventional various extraction methods.
- the ⁇ -bisabolol may be obtained using various extraction solvents, e.g., in O 0 C to 5O 0 C of extraction temperature, (a) water, (b) absolute or hydrous lower alcohol containing 1-4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) mixture of lower alcohol and water, (d) acetone, (e) ethyl acetate, (f) chloroform or (g) 1,3-butyleneglycol.
- ⁇ -bisabolol used in the present invention may be subjected to additional purification by the well-known methods in the art as well as those obtained by extraction.
- ⁇ -bisabolol obtained using a variety of additional purification methods such as ultrafiltration with defined molecular weight cut-off value and various chromatography (designed for purification dependent upon size, charge, hydrophobicity and affinity) may be used in the present invention.
- compositions of the present invention have novel use of skin whitening.
- whitening refers to improvement of skin trouble preventing skin melanism induced by melanin pigmentation.
- ⁇ -bisabolol exhibits the inhibition effect on melanin production by inhibiting intracellular tyrosinase activity compared to arbutin used as an existing skin whitening agent, and as a result, excellent efficacy in skin whitening.
- ⁇ -Bisabolol shows a high stability and no or a little side effects such as skin irritability induction. Furthermore, the content of ⁇ -bisabolol is constantly maintained in the composition. Such effects and efficacies are demonstrated in Examples described hereunder.
- compositions for improving skin condition of the present invention have novel use to improve skin wrinkles.
- the compositions of the present invention exhibit the inhibition effect on collagenase activity and promotion effect on collagen biosynthesis at a molecular level, and as a result, excellent efficacy in improvement of skin wrinkles. Such effects and efficacies are demonstrated in Examples described hereunder. It would be appreciated that the improvement of skin wrinkles covers general uses of skin protection ⁇ e.g., prevention of skin wrinkles, removal of skin wrinkles and prevention of skin aging).
- compositions for improving skin condition of this invention have alleviating, improving, preventing or treating effects on UV-induced skin damage.
- the compositions for improving skin conditions of this invention contribute very effectively to the prevention of hair loss or the promotion of hairs growth.
- hair loss prevention and hairs growth promotion used herein have the same meaning.
- ⁇ -Bisabolol as an active ingredient of the present compositions exhibit an anti- oxidation effect by eliminating free radicals effectively.
- the composition for anti-oxidation of the present invention may be applied to a variety of diseases, disorders or abnormal conditions capable of preventing or treating by inhibiting or eliminating oxidation conditions.
- the diseases associated with anti- oxidation to be treated by the present composition include neurodegenerative disorders such as atherosclerosis, coronary heart disease, restenosis, reperfusion injury, parkinson's disease or alzheimer's disease, stroke, cancer, aging, cardiovascular disorder, osteoporosis, disorder of central nervous system, peripheral vascular disease and dyspnea, but not limited to.
- the composition for anti-oxidation of this invention is used to prevention or remedy of aging.
- composition for anti-oxidation of this invention protects DNA, protein (including lipoprotein) and membrane lipid from oxidative damage by excellent effects on elimination of free radicals.
- ⁇ -bisabolol as an active ingredient of this invention has an excellent anti-obesity effect.
- ⁇ -bisabolol represented by Formula I includes derivatives obtained by chemical processes with substituents performed conventionally in one skilled in the art. The derivatives show the effects of skin whitening by inhibition of melanin synthesis and/or tyrosinase activity, or improvement in wrinkles and UV-induced skin damage, hair growth promotion or hair loss prevention, anti-oxidation and anti-obesity effects.
- ⁇ -bisabolol used as an active ingredient of this invention includes derivatives of Formula I as well as compounds of Formula I.
- the derivatives with structure of Formula I as nucleus may be obtained by chemical processes using various substituents well-known in the art. For example, it would be suggested that derivatives formed by linking hydroxyl, halo, nitro or C 1-3 alkyl group to Formula I are likely to exert effects identical or similar to ⁇ - bisabolol. These substituted derivatives may be also fall into the scope of this invention.
- the active ingredient of ⁇ -bisabolol in the composition is present in the amount of 0.00001-15.0 wt%, more preferably, 0.0001- 10 wt%, most preferably, 0.0001-5 wt% based on the total weight of the composition. If the amount of the active ingredient of ⁇ -bisabolol is lower than 0.00001 wt%, the effect of the composition may be negligible; in the case of exceeding 15.0 wt%, some adverse effects such as skin irritation and instability in formulation are very likely to occur.
- the composition of the present invention is a cosmetic composition.
- the cosmetic compositions of the present invention may contain auxiliaries as well as carrier in addition to the ⁇ -bisabolol as an active ingredient.
- auxiliaries include antioxidants, stabilizers, solubilizers, vitamins, colorants, odor improvers or mixtures of these ingredients.
- the cosmetic compositions may additionally comprise promoting materials of skin absorption to enhance the effects.
- the cosmetic compositions of this invention may be formulated in a wide variety of form, for non-limited example, including a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation and a spray.
- the cosmetic composition of the present invention can be provided in a form of skin softener (skin lotion), nutrient emulsion (milk lotion), nutrient cream, message cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, facial pack, spray or powder.
- the cosmetically acceptable carrier contained in the present cosmetic composition may be varied depending on the type of the formulation.
- the formulation of pastes, creams or gels may comprise animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc, zinc oxide or mixtures of these ingredients.
- powder or spray it may comprise lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or mixtures of these ingredients.
- Spray may additionally comprise the customary propellants, for example, chlorofluorohydrocarbons, propane/butane or dimethyl ether.
- the formulation of solution and emulsion may comprise solvent, solubilizer or emulsifier, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol oils, glycerol fatty esters, polyethylene glycol, fatty acid esters of sorbitan or mixtures of these ingredients.
- solvent solubilizer or emulsifier
- solubilizer or emulsifier for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol oils, glycerol fatty esters, polyethylene glycol, fatty acid esters of sorbitan or mixtures of these ingredients.
- the formulation of suspension may comprise liquid diluents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isosteary alcohols, polyoxyethylene sorbitol esters and poly oxyethylene sorbitan esters, micocrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these ingredients.
- liquid diluents for example water, ethanol or propylene glycol
- suspending agents for example ethoxylated isosteary alcohols, polyoxyethylene sorbitol esters and poly oxyethylene sorbitan esters, micocrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these ingredients.
- the formulation of cleansing compositions with surfactant may comprise aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosucinnate monoester, isothinate, imidazolium derivatives, methyltaurate, sarcocinate, fatty acid amide ether sulfate, alkyl amido betain, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanoline derivatives, ethoxylated glycerol fatty acid ester or mixtures of these ingredients.
- composition of this invention may be prepared as a pharmaceutical composition, and the pharmaceutically acceptable carrier as well as the active ingredient contained in the pharmaceutical composition.
- the pharmaceutically acceptable carrier which is commonly used in pharmaceutical formulations, but is not limited to, includes lactose, dextrose, sucrose, sorbitol, mannitol, starch, rubber arable, potassium phosphate, arginate, gelatin, potassium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methyl cellulose, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, and mineral oils.
- the pharmaceutical composition according to the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, and a preservative.
- a lubricant e.g., talc, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mann
- the pharmaceutical composition of this invention may be administered to mammals such as rat, mouse, domestic animals and human via various routes, for example oral administration, rectal administration or intravenous injection, intramuscular injection, subcutaneous injection, intrauterine injection or intracerebroventricular injection, preferably subcutaneous injection, more preferably topical application.
- a suitable dosage amount of the pharmaceutical composition of the present invention may vary depending on pharmaceutical formulation methods, administration methods, the patient's age, body weight, sex, pathogenic state, diet, administration time, administration route, an excretion rate and sensitivity for a used pharmaceutical composition, and physicians of ordinary skill in the art can determine an effective amount of the pharmaceutical composition for desired treatment.
- a suitable dosage unit may be administered once to several times a day with 0.001-100 mg/kg on the basis of adult.
- a suitable dosage unit may be administered by applying once to five times a day in amounts of 1.0 to 3.0 ml on the basis of adult and it has better use for more than 1 month.
- the dosage unit does not limit the scope of this invention.
- the pharmaceutical composition of the present invention may be formulated with pharmaceutically acceptable carrier and/or vehicle as described above, finally providing several forms a unit dose form and a multi-dose form.
- the formulations include, but not limited to, oral formulation such as a powder, a granule, a tablet, a capsule, a suspension, an emulsion, a syrup and an aerosol, preparation for external use such as an ointment and a cream, a suppository and sterile injection solution, and may further comprise a dispersion agent or a stabilizer.
- the composition of this invention may be prepared as a food composition.
- the food composition of this invention may comprise conventional additives for preparing food compositions, e.g., protein, carbohydrates, lipids, nutritive substances and flavors.
- Non-limiting examples of carbohydrates described above include, but not limited to, monosaccharide ⁇ e.g., glucose and fructose); disaccharide (e.g., maltose, sucrose and oligosaccharide); and polysaccharide ⁇ e.g., dextrin and cyclodextrin); and sugar alcohol (e.g., xylitol, sorbitol and erithritol).
- Non-limiting examples of Flavors include, but not limited to, natural flavors [thaumatin and extract of stevia ⁇ e.g., rebaudioside A and glycyrrhizin)] and synthetic flavors ⁇ e.g., saccharin and aspartame).
- the food composition of this invention may further comprise citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, extract of eucommia ulmoides oliv, jujube extract or extract of glycyrrhiza uralensis.
- ⁇ -bisabolol of the present invention may be used with confidence for long period due to not or a little having toxicities and side effects, particularly may be applied to cosmetic, pharmaceutical and food composition with safety as described above.
- composition of the present invention comprises ⁇ -bisabolol as an active ingredient.
- ⁇ -Bisabolol has greater skin whitening effect inhibiting melanin synthesis by inhibiting intracellular tyrosinase activities compared to arbutin used as an existing skin whitening agent.
- ⁇ -bisabolol exhibits the inhibition effect on collagenase activity and promotion effect on collagen biosynthesis at a molecular level, contributing to excellent efficacy in improvement of skin wrinkles.
- ⁇ - bisabolol indicates the improvement effects on UV-induced skin damage and the skin growth promotion or hair loss prevention. Therefore, ⁇ -bisabolol has the excellent improvement effects on skin condition.
- ⁇ -bisabolol has the excellent anti-obesity and anti-oxidation effects.
- composition of this invention can be applied to cosmetic, pharmaceutical and food composition having no cytotoxicities and side effects with safety.
- B16 mouse melanoma cells FlO (Korean Cell Line Bank) were seeded into each well of a 6-well plate (1 x 10 5 cells/well) in DMEM (Dulbecco's modified Eagle's media) containing 10% FBS (fetal bovine serum) and the cells were cultured to about more than 80% adherence by incubating in a CO 2 incubator under conditions of 37 0 C and 5.0% CO 2 . After cultivation, the medium was removed and samples were replaced in medium diluted at suitable concentration, followed by incubating for 3 days under conditions of 37 0 C and 5.0% CO 2 . The concentration of ⁇ -bisabolol was determined with 1 ppm, 5 ppm and 10 ppm, which did not show cytotoxicity.
- DMEM Dulbecco's modified Eagle's media
- FBS fetal bovine serum
- the cells removing medium were washed with PBS (phosphate buffer saline) and treated with trypsin to collect cells.
- the number of the collected cells was calculated using hematocytometer (Tiefe Depth Profondeur 0.100 mm, Paul Marienfeld GmbH & Co. KG, Germany), centrifuged at 5,000 to 10,000 rpm for 10 min and the supernatant was eliminated, thereby obtaining pellets.
- This cell pellets were dried at 6O 0 C, 100 ⁇ l of IM NaOH containing 10% DMSO was added to thereto, and intracellular melanin was obtained in incubator at 6O 0 C.
- Example 2 Inhibitory effect on tyrosinase activity by ⁇ -bisabolol
- Murine melanoma (B-16 Fl) cells were seeded into each well of a 6-well plate (1 x 10 5 cells/well) in DMEM containing 10% FBS (fetal bovine serum) and the cells were cultured to about more than 80% adherence by incubating in a CO 2 incubator under conditions of 37 0 C and 5.0% CO 2 . After cultivation, the medium was removed and samples were replaced in medium diluted at suitable concentration, followed by incubating for 3 days under conditions of 37 0 C and 5.0% CO 2 . The concentration of ⁇ - bisabolol was determined with 1 ppm, 5 ppm and 10 ppm, which did not show cytotoxicity.
- FBS fetal bovine serum
- the cells removing medium were washed with PBS (phosphate buffer saline) and treated with trypsin to collect cells.
- the number of the collected cells was calculated using hematocytometer, centrifuged at 5,000 to 10,000 rpm for 10 min and the supernatant was eliminated, thereby obtaining pellets.
- This cell pellets were lysated using lysis buffer, centrifuged at 12,000 rpm for 10 min and the supernatant was collected. Then, the cell solution was measured for absorbance at 492 nm using microplate reader and the activity of tyrosinase per cell constant number was estimated. The results were summarized in Table 2. TABLE 2
- Example 3 Evaluation of skin whitening effect in animal
- a skin whitening effect of ⁇ -bisabolol was measured using brown guinea pigs (Charles River Laboratories, Inc.) pigmentation of which is known to increase upon exposure to ultraviolet light like human.
- SE lamp wavelength 290-320 nm, Toshiba
- total irradiation energy 1350 mJ/cm 2 .
- the aluminum foil was removed and samples ( ⁇ -bisabolol or arbutin) were applied as the following method. Increased pigmentation was observed on 2-3 days after UV irradiation and reached a maximum after about 2 weeks. Following the period of time showing the maximum pigmentation, samples were applied.
- the application of samples was performed once or twice a day for 50 days.
- the control with only the solvent was applied to another site.
- the occurrence of cumulative irritation was also examined.
- the degree of pigmentation of skin was determined using a chromameter (CR2002, MINOLTA, JP) to estimate the effects of applied samples.
- the results are shown in Table 3 below.
- LVb * colorimetric system was used to classify color and L * value was used as standard in Example.
- the L * value was corrected using white board standard and was measured more than five times at one site. Pigmentation was evenly distributed. Skin color differences ( ⁇ L * ) between application starting point and application end point were obtained and used to evaluate effects of samples. The results were summarized in Table 3. Equation 1
- ⁇ L * L * value on 00 days after application - L * value on application starting day ⁇ L * values were obtained for control and sample application to evaluate skin whitening effects.
- ⁇ -bisabolol exhibited the whitening effects in concentration-dependant manner. Furthermore, it was revealed that ⁇ -bisabolol had more excellent whitening effects than arbutin as well as considerable safety that was verified by no observation of cumulative irritation.
- Example 4-1 Preparation of a skin external composition containing ⁇ - bisabolol A skin external composition containing ⁇ -bisabolol and arbutin was prepared and its safety test on human skin was performed to determine whether ⁇ -bisabolol is safe on skin.
- the skin external composition containing ⁇ -bisabolol and arbutin was prepared as indicated in Table 4.
- the control group in Table 4 is a skin external composition not containing tyrosinase inhibitor
- the test groups 1 and 2 are a skin external composition containing ⁇ -bisabolol and arbutin, respectively.
- distilled water, serine and butylene glycol were mixed and dissolved at 70 0 C (water phase) and the remaining components were dissolved at 70 0 C (oil phase).
- the oil phase was added to the water phase and agitated using a homomixer (Tokushu Kika, Japan) for first emulsification, followed by addition of trimethanolamine.
- the air bubble formed in the mixed solution was eliminated and cooled to room temperature to prepare the skin external composition.
- Example 4-1 Each skin external composition prepared in Example 4-1 was applied in patches 9 times to the upper arms of 30 healthy adults once every other day for a total time period of 24 hours. This 24-hour cumulative patch test was conducted to determine whether ⁇ -bisabolol irritates the skin or not.
- Average response level [ ⁇ (response index x response Ievel)/No. of test subjects x maximum points (4 points) ⁇ x 100] ⁇ No. of test (9 times)
- Points were marked in accordance with response level, for example, ⁇ for 1 point, + for 2 points, and ++ for four points.
- the composition can be considered safe if the average response level is less than 3.
- composition comprising ⁇ -bisabolol (Test group 1) did not show any significant cumulative irritation as either control group or the arbutin- containing composition. Therefore, it could be appreciated that ⁇ -bisabolol is a safe substance for human skin.
- Superoxide dismutase has been known as an anti-oxidation-catalyzing enzyme which converts superoxide anion into H 2 O 2 and O 2 .
- This experiment evaluates anti-oxidation activity of samples by observing removal of superoxide anion generated by xanthine oxidase.
- the experiment was performed using the kit (SOD Assay Kit- WST) purchased from Dojindo (JP) in accordance with manufacture's protocol. The experiment results were summarized in Table 6. TABLE 6
- ⁇ -bisabolol of the present invention exerted the anti- oxidation effects in concentration-dependant manner.
- the incubation volume per well was adjusted to 500 ⁇ l, 2 ⁇ l of the sample compound, which dissolved in lipopolysaccahride (1 ⁇ g/ml, Sigma) and solvents described in the following Table respectively, was added and cultivated for 24-48 hr under the same condition. After 24-48 hr, calcium ionophore (Sigma) and [1-14C] arachidonic acid 1 ⁇ l (in EtOH, 0.1 ⁇ Ci/ml, Sigma) were added to each well, and cultivated for 10 min under the same condition.
- Example 7 Evaluation of Immunosuppressive effects
- Interleukin-2 promoter was reported to play an important role in the generation of cytokine related to inflammatory.
- the activity of interleukin-2 luciferase was measured using the following method: Human T lymphocytes cell line, 1 x 10 6 of Jurkat cell (Korean Cell Line Bank) were aliquoted into each well of 6-wells, IL-2 luciferase reporter plasmid DNA (Stratagene) was transfected using superfect transfection reagent (In vitrogen).
- Example 8 Measurement of effect of ⁇ -bisabolol on wrinkles improvement
- the wrinkle improvement effect can be generally evaluated by measuring collagen biosynthesis ability and collagenase degradation inhibitory ability and performing clinical test with human.
- Human fibroblasts (commercially available from pacific) were seeded into a 6- well plate (2 x 10 5 cells/well) and the well plate was incubated in a 5% CO 2 incubator for 24 hr at 37 0 C. After 24 hr, the medium in each well was removed and cells were incubated with various concentrations of samples for 24 hr. Afterwards, the cell medium was collected and was used as samples.
- the potential of collagen synthesis was determined by measuring the amount of procollagen type I C-peptide (PICP) in cell medium using Procollagen Type I C- peptide EIA kit (MKlOl, Takara, Kyoto, Japan) in accordance with manufacturer's protocol.
- PICP procollagen type I C-peptide
- mice 7 week-old ICR male mice (obtained from Charles River Japan Ltd) weeks were preliminarily fed for 1 week, then classified into groups each having 7 animals and subjected to the test. The animals were fed under controlled conditions at a temperature of 23 ⁇ 1°C, and a humidity of 55 ⁇ 5% under illumination for 12 hours per day. They were fed with a feed Labo MR (manufactured by Nippon Nosan) and allowed to take water ad libitum.
- Labo MR manufactured by Nippon Nosan
- ⁇ -Bisabolol was present in the form of liposome (prepared with 5% lecithin) to the final concentration of either 0.1% or 1%.
- concentration of each sample solution was adjusted so that 0.1 ml of the solution was given per 10 g body weight of mice.
- the doses employed were 1.5 g/kg and 1 g/kg.
- 5% lecithin emulsion was administered. After fasting the mice, the sample was administered once by force on the next day. During the test period over 2 weeks, the body weight and general conditions were monitored.
- Example 10 Effect of hair loss prevention and hairs growth promotion
- the samples were prepared in the form of hydrogel base containing only viscosity- increasing agent and preservative, and test was performed.
- Each 3 cc of liquids for external use for promoting hairs growth prepared were applied to the hair loss sites of 10 baldness patients twice a day for 3 months.
- the liquids containing the samples showed an excellent effect such as the generation of the root of hair from 8 baldness patients.
- the experiment results were as follows.
- the control group used the moxidil commercially available from Hanmi pharmaceutical. Co. Ltd. TABLE 11
- the present invention provides a composition for improving skin condition comprising ⁇ -bisabolol as an active ingredient.
- ⁇ -Bisabolol used as an active ingredient has greater skin whitening effect inhibiting melanin synthesis by inhibiting intracellular tyrosinase activities compared to arbutin used as an existing skin whitening agent.
- ⁇ -bisabolol exhibits the inhibition effect on collagenase activity and promotion effect on collagen biosynthesis at a molecular level, contributing to excellent efficacy in improvement of skin wrinkles.
- ⁇ - bisabolol indicates the improvement effects on UV-induced skin damage and the skin growth promotion or hair loss prevention. Therefore, ⁇ -bisabolol has the excellent improvement effects on skin condition.
- ⁇ -bisabolol has the excellent anti-obesity and anti-oxidation effects.
- the composition of this invention can be applied to cosmetic, pharmaceutical and food composition having no cytotoxicities and side effects with safety.
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- Pharmacology & Pharmacy (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08723179.1A EP2124872B1 (en) | 2007-02-27 | 2008-02-27 | Improving skin conditions with alpha-bisabolol as active principle |
CN2008800061597A CN101677925B (en) | 2007-02-27 | 2008-02-27 | Compositions for improving skin conditions comprising alpha-bisabolol as an active ingrdient |
JP2009501364A JP4482060B2 (en) | 2007-02-27 | 2008-02-27 | Cosmetic composition and pharmaceutical composition for skin whitening or wrinkle improvement containing α-bisabolol as an active ingredient |
BRPI0807326-0A BRPI0807326A2 (en) | 2007-02-27 | 2008-02-27 | "COMPOSITION TO IMPROVE SKIN CONDITION, ANTIOXIDATION COMPOSITION AND ANTIOBESITY COMPOSITION" |
US12/527,756 US20100015071A1 (en) | 2007-02-27 | 2008-02-27 | Compositions for Improving Skin Conditions Comprising Alpha-Bisabolol as an Active Ingredient |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020070019899A KR100823533B1 (en) | 2007-02-27 | 2007-02-27 | COMPOSITIONS FOR IMPROVING SKIN CONDITIONS COMPRISING alpha;-BISABOLOL AS AN ACTIVE INGREDIENT |
KR10-2007-0019899 | 2007-02-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008105632A1 true WO2008105632A1 (en) | 2008-09-04 |
Family
ID=39571977
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2008/001141 WO2008105632A1 (en) | 2007-02-27 | 2008-02-27 | Compositions for improving skin conditions comprising alpha-bisabolol as an active ingrdient |
Country Status (7)
Country | Link |
---|---|
US (1) | US20100015071A1 (en) |
EP (1) | EP2124872B1 (en) |
JP (1) | JP4482060B2 (en) |
KR (1) | KR100823533B1 (en) |
CN (1) | CN101677925B (en) |
BR (1) | BRPI0807326A2 (en) |
WO (1) | WO2008105632A1 (en) |
Cited By (5)
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WO2010015487A3 (en) * | 2008-08-05 | 2010-06-10 | Unilever Plc | Skin lightening compositions comprising co2 extracts |
WO2012076352A1 (en) * | 2010-12-09 | 2012-06-14 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Composition for topical use for treating skin disorders |
WO2014149867A1 (en) * | 2013-03-15 | 2014-09-25 | The Procter & Gamble Company | Cosmetic compositions and methods for inhibiting melanin synthesis |
EP2842607A1 (en) * | 2013-09-02 | 2015-03-04 | Symrise AG | A skin and/or hair whitening mixture |
US9227090B2 (en) | 2008-06-18 | 2016-01-05 | Conopco, Inc. | Method for lightening skin |
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JP2012158554A (en) * | 2011-02-01 | 2012-08-23 | Mikimoto Pharmaceut Co Ltd | Skin care preparation |
JP6058271B2 (en) * | 2012-02-08 | 2017-01-11 | 御木本製薬株式会社 | Topical skin preparation |
KR101830599B1 (en) * | 2013-05-01 | 2018-02-22 | 더 프록터 앤드 갬블 캄파니 | Cosmetic compositions and methods for inhibiting melanin synthesis |
JP6416284B2 (en) * | 2014-04-23 | 2018-10-31 | ザ プロクター アンド ギャンブル カンパニー | Cosmetic composition with reduced irritation |
KR102008587B1 (en) * | 2014-09-12 | 2019-08-07 | 더 프록터 앤드 갬블 캄파니 | Cosmetic compositions and methods for inhibiting melanin synthesis |
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CN105496938B (en) * | 2015-12-29 | 2019-01-01 | 苏州工业园区安诺科斯化妆品研发有限公司 | α-bisabolol shin moisturizer |
KR101806847B1 (en) | 2016-06-14 | 2017-12-11 | (주)토니모리 | TiO2 - Alpha-bisabolol complex with UV-blocking and whitening effect, a preparation method thereof and a use of the same |
JP6890479B2 (en) * | 2017-06-19 | 2021-06-18 | 株式会社ミルボン | Hair composition and hair treatment method |
KR102016056B1 (en) | 2018-04-19 | 2019-08-29 | 국민대학교 산학협력단 | Method for producing bisabolol using transformed yeast |
CN109771317A (en) * | 2019-03-08 | 2019-05-21 | 唐凯 | A kind of covering composition of leucoderma and scar hickie |
CN110742833B (en) * | 2019-11-28 | 2022-08-09 | 广州环亚化妆品科技股份有限公司 | Acne-removing, whitening and anti-aging essential oil composition as well as preparation method and application thereof |
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US5750351A (en) | 1992-10-30 | 1998-05-12 | Emory University | Treatment for atherosclerosis and other cardiovascular and inflammatory diseases |
WO1998034591A1 (en) | 1997-02-11 | 1998-08-13 | The Procter & Gamble Company | Skin lightening compositions |
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WO2000062741A2 (en) | 1999-04-19 | 2000-10-26 | The Procter & Gamble Company | Skin care compositions containing combination of skin care actives |
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- 2007-02-27 KR KR1020070019899A patent/KR100823533B1/en active IP Right Grant
-
2008
- 2008-02-27 WO PCT/KR2008/001141 patent/WO2008105632A1/en active Application Filing
- 2008-02-27 BR BRPI0807326-0A patent/BRPI0807326A2/en not_active Application Discontinuation
- 2008-02-27 JP JP2009501364A patent/JP4482060B2/en active Active
- 2008-02-27 CN CN2008800061597A patent/CN101677925B/en active Active
- 2008-02-27 US US12/527,756 patent/US20100015071A1/en not_active Abandoned
- 2008-02-27 EP EP08723179.1A patent/EP2124872B1/en active Active
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WO2001047481A1 (en) | 1999-12-28 | 2001-07-05 | Pharmaskin Ltd. | Composition for the treatment of dandruff |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9227090B2 (en) | 2008-06-18 | 2016-01-05 | Conopco, Inc. | Method for lightening skin |
WO2010015487A3 (en) * | 2008-08-05 | 2010-06-10 | Unilever Plc | Skin lightening compositions comprising co2 extracts |
CN102123765A (en) * | 2008-08-05 | 2011-07-13 | 荷兰联合利华有限公司 | Skin lightening compositions comprising CO2 extracts |
WO2012076352A1 (en) * | 2010-12-09 | 2012-06-14 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Composition for topical use for treating skin disorders |
WO2014149867A1 (en) * | 2013-03-15 | 2014-09-25 | The Procter & Gamble Company | Cosmetic compositions and methods for inhibiting melanin synthesis |
EP2842607A1 (en) * | 2013-09-02 | 2015-03-04 | Symrise AG | A skin and/or hair whitening mixture |
US9889078B2 (en) | 2013-09-02 | 2018-02-13 | Symrise Ag | Skin and/or hair whitening mixture |
Also Published As
Publication number | Publication date |
---|---|
BRPI0807326A2 (en) | 2014-07-01 |
US20100015071A1 (en) | 2010-01-21 |
KR100823533B1 (en) | 2008-04-30 |
EP2124872B1 (en) | 2018-06-06 |
CN101677925B (en) | 2012-07-04 |
EP2124872A1 (en) | 2009-12-02 |
CN101677925A (en) | 2010-03-24 |
JP4482060B2 (en) | 2010-06-16 |
JP2009526870A (en) | 2009-07-23 |
EP2124872A4 (en) | 2011-12-21 |
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